Search Results (12,830)

Background: Fixed-dose combinations have advanced in many therapeutic areas, including otorhinolaryngology, where hearing disorders are increasingly prevalent. Objectives: The present study focuses on developing and evaluating a new capsule combining nicergoline (NIC), piracetam (PIR), and hawthorn extract (HE) for the management of sensorineural hearing loss. Methods: The first phase methodology comprised preformulation studies (DSC, FTIR, and PXRD) to assess compatibility among active substances and excipients. Subsequently, four formulations were prepared and tested for flowability, dissolution behavior in acidic and neutral media, and stability under oxidative, thermal, and photolytic stress. Quantification of the active substances and flavonoids was performed using validated spectrophotometric and HPLC-UV methods. Results: Among the tested variants, the F1 formulation (4.5 mg NIC, 200 mg PIR, 50 mg HE, 2.5 mg magnesium stearate, 2.5 mg sodium starch glycolate, and 240.5 mg monohydrate lactose per capsule) displayed optimal technological properties, superior dissolution in acidic media, and was further selected for evaluation. The antioxidant activity of the formulation was confirmed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, Trolox Equivalent Antioxidant Capacity (TEAC), and iron chelation tests, and was primarily attributed to the flavonoid content of the HE. Acute toxicity tests in mice and rats indicated a high safety margin (LD₅₀ > 2500 mg/kg), while ototoxicity assessments showed no adverse effects on auditory function. Conclusions: The developed formulation displayed good stability, safety, and therapeutic potential, while the applied workflow could represent a model for the development of future fixed-dose combinations. Full article

(1) Background: Rapid population aging in China intensifies physical and mental health challenges, including negative emotions and social barriers. Physical activity (PA) fosters resilience, adaptability, and successful aging through emotional and social benefits. This study examines the relationship between square-dancing exercise and psychological capital (PsyCap) in middle-aged and elderly individuals using cross-validation, subgroup analysis, and a cross-sequential design. (2) Methods: A cross-sectional study with 5714 participants employed a serial mediation model. Online questionnaires assessed square-dancing exercise, cognitive reappraisal, prosocial behavior tendencies, PsyCap, and interpersonal relationships. Statistical analyses were conducted using SPSS 27.0 and Mplus 8.3, incorporating correlation analysis, structural equation modeling, and subgroup comparisons. (3) Results: (a) Cognitive reappraisal and prosocial behavior mediated the link between square-dancing and PsyCap through three pathways; (b) model stability was confirmed across two random subsamples; (c) cross-group differences emerged in age and interpersonal relationships. Compared with secondary data, this study further validated PsyCap’s stability over six months post-pandemic. (4) Conclusions: The study, based on China’s largest square-dancing sample, establishes a robust serial mediation model. The findings strengthen theoretical foundations for PA-based interventions promoting psychological resilience in aging populations, highlighting structured exercise’s role in mental and social well-being. Full article

Thyroid cancer is the most common endocrine malignancy, and preoperative distinction between benign and malignant nodules remains challenging, especially in cytologically indeterminate cases. Circulating microRNAs (miRNAs) have gained interest as non-invasive biomarkers due to their stability and involvement in tumorigenesis. This study aimed to assess the preoperative diagnostic value of circulating miR-146a and miR-221 in patients undergoing thyroidectomy. A total of 56 patients were included, of whom 24 had malignant and 32 had benign thyroid lesions confirmed by histopathology. Preoperative plasma levels of miR-146a and miR-221 were quantified using qRT-PCR, and relative expression was calculated with the 2^−ΔΔCt method. miR-221 expression was significantly higher in malignant cases, with an area under the ROC curve of 1.00, achieving 100% sensitivity and specificity at the optimal threshold. miR-146a showed no significant discriminatory ability. Weak correlations were observed between miRNA expression and clinical parameters such as age, TIRADS score, or thyroid volume. Logistic regression including miR-221 led to perfect separation, indicating strong predictive capacity but precluding multivariate modeling. These findings suggest that circulating miR-221 may serve as a highly accurate biomarker for thyroid malignancy and warrant further validation in larger, prospective cohorts. Full article

Earthquakes, as one of the most destructive natural disasters, often cause significant casualties and severe economic losses. Accurate prediction of earthquake fatalities is of great importance for pre-disaster prevention and mitigation planning, as well as post-disaster emergency response deployment. To address the challenges of small sample sizes, high dimensionality, and strong nonlinearity in earthquake fatality prediction, this paper proposes an integrated modeling approach (PCA-IWOA-XGBoost) combining Principal Component Analysis (PCA), the Improved Whale Optimization Algorithm (IWOA), and Extreme Gradient Boosting (XGBoost). The method first employs PCA to reduce the dimensionality of the influencing factor data, eliminating redundant information and improving modeling efficiency. Subsequently, the IWOA is used to intelligently optimize key hyperparameters of the XGBoost model, enhancing the prediction accuracy and stability. Using 42 major earthquake events in China from 1970 to 2025 as a case study, covering regions including the west (e.g., Tonghai in Yunnan, Wenchuan, Jiuzhaigou), central (e.g., Lushan in Sichuan, Ya’an), east (e.g., Tangshan, Yingkou), north (e.g., Baotou in Inner Mongolia, Helinger), northwest (e.g., Jiashi in Xinjiang, Wushi, Yongdeng in Gansu), and southwest (e.g., Lancang in Yunnan, Lijiang, Ludian), the empirical results showed that the PCA-IWOA-XGBoost model achieved an average test set accuracy of 97.0%, a coefficient of determination (R²) of 0.996, a root mean square error (RMSE) and mean absolute error (MAE) reduced to 4.410 and 3.430, respectively, and a residual prediction deviation (RPD) of 21.090. These results significantly outperformed the baseline XGBoost, PCA-XGBoost, and IWOA-XGBoost models, providing improved technical support for earthquake disaster risk assessment and emergency response. Full article

To study and quantify the impact of water storage on lake slope stability after the closure of an open-pit mine, we targeted slope control measures by large-scale parallel computing methods and strength reduction theory. This was based on a three-dimensional refined numerical model to simulate the evolution of slope stability under different water storage levels and backfilling management conditions, and to quantitatively assess the risk of slope instability through the spatial distribution of stability coefficients. This study shows that during the impoundment process, the slope stability has a nonlinear decreasing trend due to the decrease in effective stress caused by the increase in pore water pressure. When the water storage was at 0 m, the instability range is the largest, and the surface range is nearly 200 m from the edge of the pit; when the water level continued to rise to 50 m, the hydrostatic pressure of the pit lake water on the slope support effect began to appear, and the stability was improved, but there is still a wide range of unstable areas at the bottom. In view of the unstable area of the steep slope with soft rock in the north slope during the process of water storage, the management scheme of backfilling the whole bottom to −150 m was proposed, and the slope protection and pressure footing were formed by discharging the soil to −40 m in steps to improve the anti-slip ability of the slope. Full article

This study investigates the predictive performance of financial indicators in forecasting stock prices within the automotive sector using an adaptive neuro-fuzzy inference system (ANFIS). In light of the growing complexity of global financial markets and the increasing demand for automated, data-driven forecasting models, this research aims to identify those financial ratios that most accurately reflect price dynamics in this specific industry. The model incorporates four widely used financial indicators, return on assets (ROA), return on equity (ROE), earnings per share (EPS), and profit margin (PM), as inputs. The analysis is based on real financial and market data from automotive companies, and model performance was assessed using RMSE, nRMSE, and confidence intervals. The results indicate that the full model, including all four indicators, achieved the highest accuracy and prediction stability, while the exclusion of ROA or ROE significantly deteriorated model performance. These findings challenge the weak-form efficiency hypothesis and underscore the relevance of firm-level fundamentals in stock price formation. This study’s sector-specific approach highlights the importance of tailoring predictive models to industry characteristics, offering implications for both financial modeling and investment strategies. Future research directions include expanding the indicator set, increasing the sample size, and testing the model across additional industry domains. Full article

Granite formations provide suitable geological conditions for building gravity dams. However, the presence of intruding granite creates a fractured zone. The interaction of this fractured zone with structural planes and faults can create geological conditions that are unfavorable for the anti-sliding stability of gravity dams. This paper identifies the dominant structural planes that affect the anti-sliding stability of dams by studying the three-dimensional intersection relationships between groups of structural planes, faults, and fracture zones. The three-dimensional distribution and occurrence of the dominant structural planes directly impact the anti-sliding stability and sliding failure mode of gravity dams. Through comprehensive field investigations and systematic analysis of engineering geological data, the spatial distribution characteristics of structural planes and fracture zones were quantitatively characterized. Subsequently, the potential for deep-seated sliding failure of the gravity dam was rigorously evaluated and conclusively dismissed through application of the rigid body limit equilibrium method. It was established that the sliding mode of the foundation of the dam under this combination of structural planes is primarily shallow sliding. Additionally, based on the engineering geological data of the area around the dam, a three-dimensional finite element numerical model was developed to analyze stress–strain calculations under seepage stress coupling conditions and compared with calculations made without considering seepage stress coupling. The importance of seepage in the anti-sliding stability of the foundation of the dam was determined. The research findings provide engineering insights into enhancing the anti-sliding stability of gravity dams in granite distribution areas by (1) identifying critical structural planes and fracture zones that control sliding behavior, (2) demonstrating the necessity of seepage-stress coupling analysis in stability assessments, and (3) guiding targeted reinforcement measures to mitigate shallow sliding risks. Full article

During the process of oil and gas drilling, due to the existence of pores or micro-cracks, drilling fluid is prone to invade the formation. Under the action of hydration expansion of clay in the formation and liquid pressure, wellbore instability occurs. In order to reduce the wellbore instability caused by drilling fluid intrusion into the formation, this study proposed a method of forming a dynamic hydrogen bond cross-linked network weak gel structure with modified nano-silica and P(AM-AAC). The plugging performance of the drilling fluid and the performance of inhibiting the hydration of shale were evaluated through various experimental methods. The results show that the gel composite system (GCS) effectively optimizes the plugging performance of drilling fluid. The 1% GCS can reduce the linear expansion rate of cuttings to 14.8% and increase the recovery rate of cuttings to 96.7%, and its hydration inhibition effect is better than that of KCl and polyamines. The dynamic cross-linked network structure can significantly increase the viscosity of drilling fluid. Meanwhile, by taking advantage of the liquid-phase viscosity effect and the physical blocking effect, the loss of drilling fluid can be significantly reduced. Mechanism studies conducted using zeta potential measurement, SEM analysis, contact angle measurement and capillary force assessment have shown that modified nano-silica stabilizes the wellbore by physically blocking the nano-pores of shale and changing the wettability of the shale surface from hydrophilic to hydrophobic when the contact angle exceeds 60°, thereby reducing capillary force and surface free energy. Meanwhile, the dynamic cross-linked network can reduce the seepage of free water into the formation, thereby significantly lowering the fluid loss of the drilling fluid. This research provides new insights into improving the stability of the wellbore in drilling fluids. Full article

Poly(vinyl chloride) (PVC) undergoes thermal degradation during processing and operation, which necessitates the use of effective thermal stabilizers. The purpose of this work is to comprehensively evaluate the potential of new hierarchically structured titanium phosphates (TiP) with controlled morphology as thermal stabilizers of plasticized PVC, focusing on the effect of morphology and Ti/P ratio on their stabilizing efficiency. The thermal stability of the compositions was studied by thermogravimetric analysis (TGA) in both inert (Ar) and oxidizing (air) atmospheres. The effect of TiP concentration and its synergy with industrial stabilizers was analyzed. An assessment of the key degradation parameters is given: the temperature of degradation onset, the rate of decomposition, exothermic effects, and the carbon residue yield. In an inert environment, TiPMSI/TiPMSII microspheres demonstrated an optimal balance by increasing the temperature of degradation onset and the residual yield while suppressing the rate of decomposition. In an oxidizing environment, TiPR rods and TiPMSII microspheres provided maximum stability, enhancing resistance to degradation onset and reducing the degradation rate by 10–15%. Key factors of effectiveness include ordered morphology (spheres, rods); the Ti-deficient Ti/P ratio (~0.86), which enhances HCl binding; and crystallinity. The stabilization mechanism of titanium phosphates is attributed to their high affinity for hydrogen chloride (HCl), which catalyzes PVC chain scission, a catalyst for the destruction of the PVC chain. The unique microstructure of titanium phosphate provides a high specific surface area and, as a result, greater activity in the HCl neutralization reaction. The formation of a sol–phosphate framework creates a barrier to heat and oxygen. An additional contribution comes from the inhibition of oxidative processes and the possible interaction with unstable chlorallyl groups in PVC macromolecules. Thus, hierarchically structured titanium phosphates have shown high potential as multifunctional PVC thermostabilizers for modern polymer materials. Potential applications include the development of environmentally friendly PVC formulations with partial or complete replacement of toxic stabilizers, the optimization of thermal stabilization for products used in aggressive environments, and the use of hierarchical TiP structures in flame-resistant and halogen-free PVC-based compositions. Full article

In the face of growing demand for food and climate change, ensuring the stability and height of crop yields is becoming a key challenge for modern agriculture. One of the solutions supporting the sustainable development of crop production is the use of certified seed. The aim of this study was to assess the impact of using certified seed on the level and stability of yields of three cereal species: winter wheat, winter triticale and spring barley, in temperate climate conditions. Data came from surveys conducted on over 8000 farms in six agroecoregions of Poland in 2021–2023. The analysis showed significantly higher yields on farms using certified seed for all species studied. Additionally, greater yield stability (lower values of Shukla variance and Wricke ecovalence) was noted in the case of using certified seeds, especially in region IV. This indicates the positive impact of certified seeds (e.g., genetic purity, health, and vigor) on the efficiency and resilience of agricultural systems. This phenomenon is of particular importance in the context of climate change and may be an important element of risk management strategies in agriculture. Full article

Background/Objectives: Trochanteric femoral fractures pose significant surgical challenges, particularly in elderly patients. Intramedullary nailing (IMN) and plate fixation (PF) are the primary operative strategies, yet their comparative efficacy and safety remain debated. This meta-analysis synthesizes randomized controlled trials (RCTs) to evaluate clinical, functional, perioperative, and biomechanical outcomes of IMN versus PF specifically in trochanteric fractures. Methods: A systematic search of six databases was conducted up to 20 May 2024, to identify RCTs comparing IMN and PF in adult patients with trochanteric femoral fractures. Data extraction followed PRISMA guidelines, and outcomes were pooled using random-effects models. Subgroup analyses examined the influence of fracture stability, implant type, and patient age. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Results: Fourteen RCTs (n = 4603 patients) were included. No significant differences were found in reoperation rates, union time, implant cut-out, or mortality. IMN was associated with significantly reduced operative time (MD = −5.18 min), fluoroscopy time (MD = −32.92 s), and perioperative blood loss (MD = −111.68 mL). It also had a lower risk of deep infection. Functional outcomes and anatomical results were comparable. Subgroup analyses revealed fracture stability and nail type significantly modified operative time, and compression screws were associated with higher reoperation rates than IMN. Conclusions: For trochanteric femoral fractures, IMN and PF yield comparable results for most clinical outcomes, with IMN offering some advantages in surgical efficiency and perioperative morbidity, though functional outcomes were comparable. Implant selection and fracture stability influence outcomes, supporting individualized surgical decision making. Full article

The global spread of Mpox virus (MPXV) underscores the urgent need for rapid, field-deployable diagnostic tools, especially in low-resource settings. We evaluated a loop-mediated isothermal amplification (LAMP) assay, termed LAMPOX, developed by Coris BioConcept. The assay was tested in three formats—two liquid versions and a dried, ready-to-use version—targeting only the ORF F3L (Liquid V1) or both the ORF F3L and N4R (Liquid V2 and dried) genomic regions. Analytical sensitivity and specificity were assessed using 60 clinical samples from confirmed MPXV-positive patients. Sensitivity on clinical samples was 81.7% for Liquid V1 and 88.3% for Liquid V2. The dried LAMPOX assay demonstrated a sensitivity of 88.3% and a specificity of 100% in a panel of 112 negative controls, with most positive samples detected in under 7 min. Additionally, a simplified sample lysis protocol was developed to facilitate point-of-care use. While this method showed slightly reduced sensitivity compared to standard DNA extraction, it proved effective for samples with higher viral loads. The dried format offers key advantages, including ambient-temperature stability and minimal equipment needs, making it suitable for point-of-care testing. These findings support LAMPOX as a promising tool for rapid MPXV detection during outbreaks, especially in resource-limited settings where traditional PCR is impractical. Full article

Land use conversion to perennial cropland often degrades the soil structure and fertility, particularly under Mediterranean climatic conditions. This study assessed spatial and temporal dynamics of soil properties and tree responses to 3-year repeated mature compost additions in a citrus orchard. Digital soil mapping revealed strong baseline heterogeneity in texture, CEC, and Si pools. Compost application markedly increased total organic C and N levels, aggregate stability, and pH with noticeable changes after the first amendment, whereas a limited C storage potential was found following further additions. NDVI values of tree canopies monitored over a 3-year period showed significant time-dependent changes not correlated with the soil fertility variables, thus suggesting that multiple interrelated factors affect plant responses. The non-crystalline amorphous Si/total amorphous Si (_iSi:Si_amor) ratio is here proposed as a novel indicator of pedogenic alteration in disturbed agroecosystems. These findings highlight the importance of tailoring organic farming strategies to site-specific conditions and reinforce the value to combine C and Si pool analysis for long-term soil fertility assessment. Full article

This study presents the scientific and methodological foundation of Spain’s first national framework for the ethical management of community cat populations: the Action Plan for the Management of Community Cat Colonies (PACF), launched in 2025 under the mandate of Law 7/2023. This pioneering legislation introduces a standardized, nationwide obligation for trap–neuter–return (TNR)-based management of free-roaming cats, defined as animals living freely, territorially attached, and with limited socialization toward humans. The PACF aims to support municipalities in implementing this mandate through evidence-based strategies that integrate animal welfare, biodiversity protection, and public health objectives. Using standardized data submitted by 1128 municipalities (13.9% of Spain’s total), we estimated a baseline population of 1.81 million community cats distributed across 125,000 colonies. These data were stratified by municipal population size and applied to national census figures to generate a model-ready demographic structure. We then implemented a stochastic simulation using Vortex software to project long-term population dynamics over a 25-year horizon. The model integrated eight demographic–environmental scenarios defined by a combination of urban–rural classification and ecological reproductive potential based on photoperiod and winter temperature. Parameters included reproductive output, mortality, sterilization coverage, abandonment and adoption rates, stochastic catastrophic events, and territorial carrying capacity. Under current sterilization rates (~20%), our projections indicate that Spain’s community cat population could surpass 5 million individuals by 2050, saturating ecological and social thresholds within a decade. In contrast, a differentiated sterilization strategy aligned with territorial reproductive intensity (50% in most areas, 60–70% in high-pressure zones) achieves population stabilization by 2030 at approximately 1.5 million cats, followed by a gradual long-term decline. This scenario prioritizes feasibility while substantially reducing reproductive output, particularly in rural and high-intensity contexts. The PACF combines stratified demographic modeling with spatial sensitivity, offering a flexible framework adaptable to local conditions. It incorporates One Health principles and introduces tools for adaptive management, including digital monitoring platforms and standardized welfare protocols. While ecological impacts were not directly assessed, the proposed demographic stabilization is designed to mitigate population-driven risks to biodiversity and public health without relying on lethal control. By integrating legal mandates, stratified modeling, and realistic intervention goals, this study outlines a replicable and scalable framework for coordinated action across administrative levels. It exemplifies how national policy can be operationalized through data-driven, territorially sensitive planning tools. The findings support the strategic deployment of TNR-based programs across diverse municipal contexts, providing a model for other countries seeking to align animal welfare policy with ecological planning under a multi-level governance perspective. Full article

Liposomes (LPs) represent one of the most effective nanoscale platforms for drug delivery in cancer therapy due to their favorable pharmacokinetic and various body tissue compatibility profiles. Building on recent findings showing that carbon dots derived from N-hydroxyphthalimide (CDs-NHF) possess intrinsic antitumor activity, herein, we investigate the possibility of preparing complex nano-platforms composed of LPs encapsulating CDs-NHF and/or doxorubicin (DOX) for breast and lung cancer. Various LP formulations were prepared and characterized using Cryo-TEM and Cryo-SEM for morphological analysis, while zeta potential and fluorescence assessments confirmed their stability and optical properties. Cellular effects were evaluated through immunofluorescence microscopy and proliferation assays. LPs-CDs-NHF significantly reduced cancer cell viability at lower concentrations compared to free CDs-NHF, and this effect was further amplified when combined with doxorubicin. Mechanistically, the liposomal formulations downregulated key signaling molecules including pAKT, pmTOR, and pERK, indicating the disruption of cancer-related pathways. These findings suggest that LPs containing CDs-NHF, either alone or in combination with DOX, exhibit synergistic antitumor activity and hold strong promise as multifunctional nanocarriers for future oncological applications. Full article